This study projects the hydrological cycle in the Tana River Basin, Kenya, under a changing climate due to anthropogenic greenhouse gas emissions in the late 21st century, using a 20-km mesh atmospheric global climate model (AGCM) and a 0.5°–mesh global river-routing model. In addition, 60-km mesh AGCM ensemble experiments forced with four different projected sea-surface temperatures were performed to quantify the uncertainty in the climate projections. All four climatological annual mean hydroclimate variables: precipitation, evaporation, total runoff, and soil water storage: are projected to increase in the future climate. With the exception of total runoff and river discharge in the headwater basin, these climatological annual mean increases are generally robust. The four climatological monthly mean hydroclimate variables at Garissa are projected to exhibit different seasonal changes. The long rains season is projected to have almost the same peak precipitation amount in April with an earlier onset, while the short rains season is projected to have significant precipitation increases. River discharges are projected to increase significantly in November to March with high consistent change in sign and in June. These results should guide the awareness programs of the changing hydrological cycles in the Tana River Basin and assist in formulating mitigation and adaptation strategies to meet these challenges.